Experimental autoimmune uveitis (EAU) is a well-established model of human intraocular inflammatory diseases or uveitis and is easily induced in susceptible animal species by immunization with retinal proteins such as interphotoreceptor retinoid binding protein (IRBP) and S-Antigen (SAg). Mice are generally resistant to EAU, but most rat strains are susceptible. Knowledge about the basic mechanisms underlying resistance to EAU or tolerance induction to ocular proteins may prove beneficial for the treatment or prevention of ocular inflammatory diseases. In fiscal year 1995-96, we sought to determine whether immunopathogenic retinal proteins are expressed in the thymus. We examined mouse, rat, and human thymi for expression of SAg and IRBP by the very sensitive reverse transcribed polymerase chain reaction (RT-PCR) assay and western blot analysis. Our goal was to determine whether there is a correlation between thymic expression of IRBP or SAg and resistance to uveitis. The traditional view is that the eye is an immunologically privileged organ and that the expression of lens and retinal proteins is segregated from the immune system and restricted to the intraocular environment. So, we were very surprised to detect both SAg and IRBP mRNA transcripts and proteins in the mouse thymus. However, the most remarkable finding in this study is the complete absence of detectable SAg or IRBP transcripts in the thymus of the Lewis, Sprague Dawley, or Brown Norway rats by the very sensitive RT-PCR assay. We also analyzed human thymi for expression of SAg or IRBP by the RT-PCR assay. Although we could not detect IRBP transcripts in human thymus, very low-level transcription of the SAg gene was detected. These results suggest that rats and humans may be susceptible to noninfectious autoimmune uveitis because of failure to establish central tolerance to the ocular autoantigens in these species. Our results also provide compelling evidence that the transcriptional machinery of the thymus is extremely permissive to the expression of genes hitherto considered to be tissue-specific; defects in thymic expression of a particular protein may be an important predisposing factor to the development of organ-specific autoimmune disease.